Fig. 6: Loss of EmKCs increases hypercholesterolemia and favors atherosclerosis development.

A Experimental strategy used to deplete EmKCs in the context of hypercholesterolemia (n = 7 mice for bDT and n = 6 mice for DT). B Total KC and (C) EmKCs (****p < 0.0001) and MoKCs (***p = 0.0002) numbers in livers of Cd207-DTR × Ldlr−/− male mice after 8 days of HC diet and injected either with bDT or DT. D Percentage of MoKCs (****p < 0.0001), E bodipy staining of EmKCs (*p = 0.049) and MoKCs (*p = 0.034), F numbers for liver monocytes and neutrophils, and (G) plasma cholesterol concentrations after 8 days HC diet feeding (1 independent experiment; **p = 0.0033). H Hepatic production of VLDLs in Cd207-DTR × Ldlr−/− mice 8 days post-injection of DT (n = 5) or bDT (n = 5) and HC diet feeding (2 independent experiments combined). Plasma triglycerides (TG) were measured overtime after p407 injection (intravascular lipolysis inhibition). I Experimental strategy. J Total KC (*p = 0.044) and (K) EmKCs (**p = 0.0027) and MoKCs numbers in livers of Cd207-DTR × Ldlr−/− female mice after 4 weeks of HC diet and injected either with bDT (n = 9) or DT (n = 9) (2 independent experiments combined). L Percentage of MoKCs (****p < 0.0001) and (M) plasma cholesterol concentrations (***p = 0.0009) after 4 weeks HC diet feeding. N The list of significantly downregulated genes (RNA-Seq) in livers of DT-treated mice as compared to bDT-treated controls was submitted to Enrichr for transcription factor enrichment analysis (ChEA_2022). O Heat map showing fold-changes in cholesterol biosynthesis intermediates in livers of DT-treated mice (n = 9) as compared to bDT-treated animals (n = 9). Differences in cholesterol (*p = 0.048) and cholesteryl-esters liver (*** < 0.001) concentrations between the two-groups are shown. P Liver content in primary (I) and secondary (II) bile acids. Fold-change for specific I and II bile acids species in livers of DT-treated mice (n = 5) as compared to bDT-treated (n = 5) animals provided as a heat map. Q Hepatic damage (ALT) in Cd207-DTR × Ldlr−/− female mice injected with bDT (n = 10) or DT (n = 11) (2 independent experiments combined) after 4 weeks of HC diet feeding. R Bile acids (I BA: *p = 0.043 and II BA: *p = 0.032) and (S) cholesterol contents in feces for both groups (n = 6 in each group) were also determined. T Representative images of atherosclerosis in the aortic root of Cd207-DTR × Ldlr−/− mice after 4 weeks of HC diet and injected either with bDT or DT. Lipid lesions were quantified by ORO staining in female (n = 6 in each group; 2 independent experiments combined; **p = 0.008) and male mice (DT, n = 9 and bDT, n = 11; 4 independent experiments combined; *p = 0.013). U Plasma cholesterol (*p = 0.05) and arterial lipid lesions (*p = 0.05) of Cd207-DTR × Ldlr−/− female mice after 2 months of HC diet and injected either with bDT (n = 7) or DT (n = 7) (2 independent experiments combined). All data in this figure are presented as mean values ± SEM. Statistical significance has been assessed with a two-sided t-test (or multiple comparison t-tests). Source data are provided as a Source Data File.